RESUMO
BACKGROUND: Although R0 surgery is recommended for stage IV colorectal cancer, the degree of required lymphadenectomy has not been established. The aim of this study was to investigate the prognostic impact of high ligation (HL) of the feeding artery and the number of retrieved lymph nodes after R0 surgery for colorectal cancer and synchronous colorectal cancer liver metastasis (CRLM). METHODS: This was a multi-institutional retrospective analysis of patients with colorectal cancer and synchronous CRLM who had R0 surgery between January 1997 and December 2007. Clinical and pathological features were compared in patients who underwent HL and those who had a low ligation (LL). Kaplan-Meier analysis was performed to estimate the effect of HL on overall survival (OS). The impact of several risk factors on survival was analysed using the Cox proportional hazards model. RESULTS: Of 549 patients, 409 (74·5 per cent) had HL. Median follow-up was 51·4 months. HL significantly improved the 5-year OS rate (58·2 per cent versus 49·3 per cent for LL; P = 0·017). Multivariable analysis revealed HL to be a significant prognostic factor compared with LL (5-year mortality: hazard ratio (HR) 0·68, 95 per cent c.i. 0·51 to 0·90; P = 0·007). In subgroup analysis, the positive effect of HL on OS was greatest in patients with lymph node metastasis. CONCLUSION: HL of the feeding artery was associated with improved OS in patients with colorectal cancer and synchronous CRLM after R0 surgery.
ANTECEDENTES: Aunque se recomienda una cirugía R0 para el cáncer colorrectal (colorectal cancer, CRC) en estadio IV, no se ha establecido el grado de linfadenectomía requerida. El objetivo de este estudio fue investigar el impacto pronóstico de la ligadura alta (high ligation, HL) de la arteria que irriga el tumor y el número de ganglios linfáticos (lymph nodes, LN) identificados después de cirugía R0 en pacientes con cáncer colorrectal y metástasis hepáticas sincrónicas (colorectal cancer liver metastasis, CRLM). MÉTODOS: En este estudio se realizó un análisis retrospectivo multicéntrico de pacientes con CRC y CRLM sincrónicas en los que se realizó una cirugía R0 desde enero de 1997 hasta diciembre de 2007. Se compararon las características clínicas y patológicas entre los pacientes a los que, durante la cirugía R0, se practicó una HL frente a los que no se practicó esta técnica. El análisis de Kaplan-Meier se realizó para estimar el efecto de la HL en la supervivencia global (overall survival, OS). El impacto de varios factores de riesgo sobre la supervivencia se analizó utilizando el modelo de Cox de riesgo proporcional. RESULTADOS: Sobre un total de 549 pacientes, se realizó una HL en 409 (74,5%), y el período de seguimiento medio en esta cohorte fue de 51,4 meses. La HL mejoró significativamente la tasa de OS a los 5 años (HL 37,7% versus no HL 27,1%, P = 0,02). El análisis multivariable mostró que la HL era un factor pronóstico significativo en comparación con la no realización de una HL (cociente de riesgos instantáneos, hazard ratio, HR de muerte a 5 años = 0,68 (i.c. del 95% 0,51-0,90), P < 0,01)). En el análisis de subgrupos, el efecto positivo de la HL sobre la OS fue mayor en pacientes con metástasis ganglionares. CONCLUSIÓN: La ligadura alta de la arteria que irriga el tumor se asoció con una mejor OS en pacientes con CRC y CRLM sincrónicas después de una cirugía R0.
Assuntos
Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Ligadura/métodos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Idoso , Neoplasias Colorretais/mortalidade , Feminino , Hepatectomia , Humanos , Japão/epidemiologia , Neoplasias Hepáticas/mortalidade , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de SobrevidaRESUMO
Dental adhesives are vital for the success of dental restorations. The objective of this study is to make strong and durable dental adhesives that are free from 2 symbolic methacrylate-based dental resins-2-bis[4-(2-hydroxy-3-methacryl-oxypropoxy)-phenyl]-propane (Bis-GMA) and 2-hydroxyethyl-methacrylate (HEMA)-and have equivalent/improved bonding strength and durability. We formulated, prepared, and evaluated 2 dental adhesives using mixtures of a hydrolytically stable ether-based monomer, triethylene glycol divinylbenzyl ether (TEG-DVBE), with urethane dimethacrylate (UDMA) or pyromellitic glycerol dimethacrylate. These adhesives were composed of equimolar ester-/ether-based vinyl functional groups. They were compared with Bis-GMA/HEMA-based commercial and experimental dental adhesives in terms of shear bond strength and microtensile bond strength (µTBS) to human dentin and the µTBS bond stability under extended thermocycling challenges. In addition, the resins' infiltration to dentin tubules, mechanical performance, and chemical properties were assessed by scanning electron microscopy, ISO standard flexural strength and modulus measurements, contact angle measurements, and water sorption/solubility measurements. The hybrid TEG-DVBE-containing dental adhesives generated equivalent shear bond strength and µTBS in comparison with the controls. Significantly, these adhesives outperformed the controls after being challenged by 10,000 thermocycles between 5 °C and 55 °C. Water contact angle measurements suggested that the hybrid dental adhesives were relatively more hydrophobic than the Bis-GMA/HEMA controls. However, both TEG-DVBE-containing adhesives developed more and deeper resin tags in dentin tubules and formed thicker hybrid layers at the composite-dentin interface. Furthermore, the water solubility of UDMA/TEG-DVBE resins was reduced approximately 89% in comparison with the Bis-GMA/HEMA controls. The relatively hydrophobic adhesives that achieved equivalent/enhanced bonding performance suggest great potentials in developing dental restoration with extended service life. Furthermore, the TEG-DVBE-containing materials may find wider dental applications and broader utility in medical device development.
Assuntos
Resinas Compostas , Colagem Dentária , Cimentos Dentários , Adesivos Dentinários , Cimentos Dentários/química , Dentina , Éter , Humanos , Teste de Materiais , Metacrilatos , Cimentos de Resina , Resistência à TraçãoRESUMO
A recent genome-wide association study identified seven single-nucleotide polymorphisms (SNPs) in region 16q24, near the Forkhead box-F1 (FOXF1) gene, which confer susceptibility to esophageal adenocarcinoma. We examined whether these SNPs are associated with clinical outcomes in gastric cancer (GC) patients in Japan and the United States. A total of 362 patients were included in this study: 151 Japanese GC patients treated with first-line S1 plus CDDP (training cohort) and 211 GC patients from Los Angeles County (LAC; validation cohort). Genomic DNA was isolated from whole blood or tumor tissue and analyzed by PCR-based direct DNA sequencing. Cox proportional hazard regression analyses were used to assess relationships between FOXF1 SNPs and progression-free survival (PFS) and overall survival (OS). FOXF1 rs3950627 was significantly associated with survival in both the training and validation cohorts. Japanese patients with the C/C genotype had a longer PFS (median 8.2 vs 5.3 months, hazard ratio (HR) 1.44, P=0.037) and OS (median 16.4 vs 12.2 months, HR 1.44, P=0.043) compared to patients with any A allele. Similarly, LAC patients with the C/C genotype had improved OS (3.9 vs 2.3 years, HR 1.5, P=0.022). Subgroup analyses showed these associations were specific to male patients and primary tumor subsite. Our findings suggest that FOXF1 rs3950627 might be a promising prognostic marker in GC patients.
Assuntos
Fatores de Transcrição Forkhead/genética , Polimorfismo de Nucleotídeo Único/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Adolescente , Adulto , Idoso , California/epidemiologia , Estudos de Casos e Controles , Feminino , Estudo de Associação Genômica Ampla/métodos , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/epidemiologia , Adulto JovemRESUMO
In this study, we investigated the differences in physical activity before and after transplantation, and the relationship between physical activity and physical function and health-related quality of life (QOL) in 30 patients who underwent allogeneic haematopoietic stem cell transplantation (allo-HSCT). Duration and intensity of physical activity were quantified using a three-dimensional accelerometer. Physical function was quantified by handgrip and knee-extensor strength, with the 6-minute walk test (6MWT) used as a measure of exercise capacity. Health-related QOL was assessed using the 36-item Short-Form Health Survey. The proportion of daily activities performed at an intensity >3.0 metabolic equivalents (METs) increased significantly after allo-HSCT (p < .05). Daily activity time performed at an intensity of 1.6-2.9 METs significantly correlated only with left knee strength (p < .05). In contrast, the total number of daily steps and the proportion of activity performed at 1.6-2.9 METs and >3.0 METs were positively correlated with the 6MWT (p < .05). Additionally, physical functioning and general health subscales in health-related QOL positively correlated with daily activities performed at >3.0 METs (p < .05). Physical activity was associated with 6MWT and health-related QOL. These findings have implications for rehabilitation planning for patients undergoing allo-HSCT.
Assuntos
Exercício Físico/fisiologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Adulto , Feminino , Força da Mão/fisiologia , Nível de Saúde , Humanos , Masculino , Força Muscular/fisiologia , Modalidades de Fisioterapia , Estudos Prospectivos , Qualidade de Vida , Transplante HomólogoRESUMO
Colorectal brain metastases (BM) are rare (1-2%) and a late-stage disease manifestation. Molecular mechanisms for BM development are not well understood. We tested whether variants within genes involved in overcoming the blood-brain barrier (BBB) are associated with BM susceptibility and survival in patients with BM. Germline single-nucleotide polymorphisms (SNPs, n=17) in seven genes (CXCR4, MMP9, ST6GALNAC5, ITGAV, ITGB1, ITGB3, KLF4) were analyzed from germline DNA in patients with resected BM (n=70) or no clinical evidence of BM after at least 24 months from diagnosis (control group, n=45). SNPs were evaluated for association with BM susceptibility and overall survival (OS) from BM diagnosis. ST6GALNAC5 rs17368584 and ITGB3 rs3809865 were significantly associated with BM susceptibility. In multivariable analysis adjusted for patient characteristics, KLF4 rs2236599, ITGAV rs10171481, ST6GALNAC5 rs1883778, CXCR4 rs2680880 and ITGB3 rs5918 were significant for OS. This study shows for the first time that variants within genes involved in breaching the BBB are associated with BM susceptibility and survival. These findings warrant further validation to develop better screening guidelines and to identify novel therapy targets for patients with BM.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundário , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Barreira Hematoencefálica/patologia , Neoplasias Encefálicas/mortalidade , Distribuição de Qui-Quadrado , Neoplasias Colorretais/mortalidade , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Heterozigoto , Homozigoto , Humanos , Estimativa de Kaplan-Meier , Fator 4 Semelhante a Kruppel , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fenótipo , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de TempoRESUMO
We analyzed associations between CXCR4/CXCL12 single-nucleotide polymorphisms and outcomes in metastatic colorectal cancer (mCRC) patients who underwent first-line bevacizumab-based chemotherapy. A total of 874 patients were included in this study: 144 treated with bevacizumab and FOLFOX or XELOX (training cohort), 653 treated with bevacizumab and FOLFIRI or FOLFOXIRI (validation cohort A or B) and 77 treated with cetuximab- and oxaliplatin-based regimens (control cohort). One CXCR4 polymorphism (rs2228014) and two CXCL12 polymorphisms (rs1801157 and rs3740085) were analyzed by PCR-based direct sequencing. Patients with a C/C genotype had a prolonged progression-free survival (PFS) compared with those with any T allele (P=0.030) in the training cohort. Similarly, patients with the C/C genotype had a superior PFS in the validation cohorts, but not in the control cohort. Our findings suggest that a common genetic variant, CXCR4 rs2228014, could predict PFS and may guide therapeutic decisions in mCRC patients receiving first-line bevacizumab-based chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Polimorfismo de Nucleotídeo Único , Receptores CXCR4/genética , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/administração & dosagem , Estudos de Coortes , Neoplasias Colorretais/tratamento farmacológico , Intervalo Livre de Doença , Feminino , Genótipo , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Valor Preditivo dos TestesRESUMO
The Hippo pathway regulates tissue growth and cell fate. In colon cancer, Hippo pathway deregulation promotes cellular quiescence and resistance to 5-Fluorouracil (5-Fu). In this study, 14 polymorphisms in 8 genes involved in the Hippo pathway (MST1, MST2, LATS1, LATS2, YAP, TAZ, FAT4 and RASSF1A) were evaluated as recurrence predictors in 194 patients with stages II/III colon cancer treated with 5-Fu-based adjuvant chemotherapy. Patients with a RASSF1A rs2236947 AA genotype had higher 3-year recurrence rate than patients with CA/CC genotypes (56 vs 33%, hazard ratio (HR): 1.87; P=0.017). Patients with TAZ rs3811715 CT or TT genotypes had lower 3-year recurrence rate than patients with a CC genotype (28 vs 40%; HR: 0.66; P=0.07). In left-sided tumors, this association was stronger (HR: 0.29; P=0.011) and a similar trend was found in an independent Japanese cohort. These promising results reveal polymorphisms in the Hippo pathway as biomarkers for stages II and III colon cancer.The Pharmacogenomics Journal advance online publication, 15 September 2015; doi:10.1038/tpj.2015.64.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias do Colo/genética , Recidiva Local de Neoplasia , Polimorfismo de Nucleotídeo Único , Transdução de Sinais/genética , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Aciltransferases , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , California , Quimioterapia Adjuvante , Colectomia , Neoplasias do Colo/patologia , Neoplasias do Colo/terapia , Feminino , Fluoruracila/uso terapêutico , Estudos de Associação Genética , Predisposição Genética para Doença , Heterozigoto , Homozigoto , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fenótipo , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores de Tempo , Tóquio , Resultado do TratamentoRESUMO
BACKGROUND: Tumor-associated macrophages (TAMs) with the M2-like phenotype are regulated by mainly NF-kB pathway including TBK1, which can influence tumor progression by secretion of proangiogenic factors such as vascular endothelial growth factor. The CCL2/CCR2 axis, histidine-rich glycoprotein (HRG), and placenta growth factor (PIGF) play a critical role in the polarization of M1/M2 phenotypes and the recruitment of TAMs to tumor microenvironment. We therefore hypothesized that variations in genes involved in regulating TAMs may predict clinical outcomes of bevacizumab treatment in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: We analyzed genomic DNA extracted from samples of patients receiving bevacizumab plus FOLFIRI as a first-line treatment using PCR-based direct sequencing. Twelve functional single-nucleotide polymorphisms in eight genes (CCL2, CCR2, HRG, PIGF, NFKB1, TBK1, CCL18, and IRF3) were tested for associations with clinical outcomes in a discovery cohort of 228 participants in TRIBE trial (NCT00719797), then validated in 248 KRAS exon2 (KRAS) wild-type participants in FIRE3 trial (NCT00433927). FIRE3-cetuximab cohort served as a negative control. RESULTS: TBK1 rs7486100 was significantly associated with overall survival in 95 KRAS wild-type patients of TRIBE cohort in univariate analysis and had a strong trend in multivariable analysis; furthermore, the association of the T allele was observed for progression-free survival (PFS) in both univariate and multivariable analyses in FIRE3-bevacizumab but not cetuximab cohort. CCL2 rs4586, CCL18 rs14304, and IRF3 rs2304205 had univariate and multivariable correlations with PFS in KRAS mutant patients of the TRIBE cohort, whereas they had no correlations in KRAS wild-type patients of the TRIBE cohort. No association was seen in control cohort. CONCLUSIONS: Our study demonstrates for the first time that variations in genes regulating TAMs-related functions are significantly associated with clinical outcomes in mCRC patients treated with bevacizumab-containing chemotherapy. These results also suggest that some TAM-related gene variations may predict outcomes of bevacizumab treatment in KRAS status-dependent manner.
Assuntos
Bevacizumab/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Variação Genética/genética , Macrófagos/fisiologia , Adulto , Idoso , Estudos de Coortes , Neoplasias Colorretais/diagnóstico , Feminino , Variação Genética/efeitos dos fármacos , Humanos , Macrófagos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Although numerous studies on Functional Independence Measure (FIM) analysis in stroke, orthopedic disease, and spinal cord injury patients have been conducted, it has rarely been done in patients undergoing cardiac rehabilitation (CR). AIM: To verify whether the Functional Independence Measure (FIM) score, and its subscale motor FIM and cognitive FIM, during inpatient CR can be a predictor of a patient's readiness for home discharge by establishing an FIM cutoff value. DESIGN: A retrospective, observational cohort study SETTING: This study was conducted at a long-term acute-care hospital. POPULATION: Participants were in-hospital patients undergoing CR (N.=949). METHODS: Measurements included motor FIM, cognitive FIM, CR period, FIM gain per week, and discharge disposition. The strongest predictor for home discharge was analyzed by using multiple logistic regression analysis, and the cutoff value of the FIM score for home discharge was determined by using receiver operating characteristic (ROC) curves. RESULTS: Discharge to home was possible in 723 patients (76.2%), whereas 226 patients (23.8%) had other outcomes. In univariate analysis, a motor FIM gain per week of five points was achieved in the home discharge group. Multiple logistic regression analysis revealed that Body Mass Index, number of comorbidities, motor FIM at discharge, cognitive FIM gain, and CR period were predictive factors with 89.6% predictive ability. ROC curve analysis showed that the cutoff value was a discharge motor FIM score of 63/64 points with 0.912 areas under the curve. CONCLUSION: Discharge motor FIM and cognitive FIM gain were predictive factors for home discharge. A motor FIM gain per week of five points and discharge motor FIM score of 64 points at the end of inpatient CR may be important predictors of a patient's readiness for discharge to home. CLINICAL REHABILITATION IMPACT: The findings of this study indicate an alternative goal to the activities of daily living in inpatients with cardiovascular disease.
Assuntos
Reabilitação Cardíaca , Cognição , Avaliação da Deficiência , Destreza Motora , Alta do Paciente , Recuperação de Função Fisiológica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Tumor dormancy has been described as a state of hibernation. Dormancy can be switched to proliferation by different pathways, which may play a critical role in tumor recurrence. In this study, we investigated genetic variations within genes involved in tumor dormancy and their association with recurrence and outcome in patients with colorectal liver metastases (CLM) who underwent neoadjuvant bevacizumab-based chemotherapy. PATIENTS AND METHODS: Genomic DNA was extracted from resected CLM (FFPE) from 149 patients. Single-nucleotide polymorphisms (SNPs) in 14 genes associated with dormancy were analyzed by direct Sanger DNA sequencing and evaluated for response, recurrence-free survival (RFS), overall survival (OS) and recurrence patterns. RESULTS: NME1 rs34214448 C>A was significantly associated with RFS in univariable analysis (P = 0.039) and with intrahepatic recurrence (P = 0.014). NOTCH3 rs1044009 T>C and CD44 rs8193 C>T showed a significant difference in 3-year OS rates (P = 0.004 and P = 0.042, respectively). With respect to radiological response, CD44 rs8193 C>T variant genotypes were associated with a significantly higher response rate (P = 0.033). Recursive partitioning analyses revealed that Dll4 rs12441495 C>G, NME1 rs34214448 C>A and NOTCH3 rs1044009 T>C were the dominant SNPs predicting histological response, RFS and OS, respectively. CONCLUSION: Our data suggest that gene variations within genes involved in tumor dormancy pathways are associated with response and outcome in patients with resected CLM. These data may lead to new and more effective treatment strategies targeting tumor dormancy.
Assuntos
Carcinoma/genética , Neoplasias Colorretais/genética , Neoplasias Hepáticas/genética , Proteínas Adaptadoras de Transdução de Sinal , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas de Ligação ao Cálcio , Carcinoma/secundário , Carcinoma/cirurgia , Neoplasias Colorretais/patologia , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Humanos , Receptores de Hialuronatos/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Metastasectomia , Pessoa de Meia-Idade , Nucleosídeo NM23 Difosfato Quinases/genética , Polimorfismo de Nucleotídeo Único , Prognóstico , Receptor Notch3 , Receptores Notch/genéticaRESUMO
In patients with colorectal liver metastases (CLM), liver resection offers the possibility of cure and long-term survival. The liver is a highly immunogenic organ harboring ~80% of the body's tissue macrophages. Emerging data demonstrate a critical role of the immune response for cancer treatment. We investigated variations within genes involved in immune response checkpoints and their association with outcomes in patients with CLM who underwent neoadjuvant chemotherapy including bevacizumab and liver resection. Single-nucleotide polymorphisms (SNPs) in nine genes (CCL2, CCR2, LAG3, NT5E, PDCD1, CD274, IDO1, CTLA4 and CD24) were analyzed in genomic DNA from 149 patients with resected bevacizumab-pretreated CLM by direct Sanger DNA sequencing, and correlated with response, recurrence-free survival (RFS), overall survival (OS), probability of cure and recurrence patterns. IDO1 (indoleamine 2, 3-dioxygenase) rs3739319 G>A and CD24 rs8734 G>A showed a significant difference in 3-year OS rates. In addition, IDO1 rs3739319 G>A was significantly associated with extrahepatic recurrence. Recursive partitioning analyses revealed that IDO1 rs3739319 G>A was the dominant SNP predicting RFS and OS. Our data suggest that variants within genes involved in immune response checkpoints are associated with outcomes in patients with resected CLM and might lead to improved treatment strategies modulating anti-tumor immune response by targeting novel immune checkpoints.
Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Genes MHC da Classe II/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Polimorfismo de Nucleotídeo Único/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Quimioterapia Adjuvante/métodos , Neoplasias Colorretais/tratamento farmacológico , Intervalo Livre de Doença , Feminino , Hepatectomia/métodos , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Prognóstico , Taxa de SobrevidaRESUMO
BACKGROUND: Nuclear factor-kappaB (NF-κB) and CCL2/CCR2 chemokine axis play a central role in tumor progression such as stimulation of angiogenesis, acceleration of tumor invasion and migration, and suppression of innate immunosurveillance in the macrophage-related functions. There have been few reports regarding association of the macrophage function-related genes with the clinical outcome in gastric cancer. We hypothesized that variants in genes encoding for NF-κB and CCL2/CCR2 axis may predict prognosis in gastric cancer and tested whether the functional single-nucleotide polymorphisms (SNPs) will be associated with clinical outcome in patients with gastric cancer across two independent groups. PATIENTS AND METHODS: This study enrolled two cohorts which consisted of 160 Japanese patients and 104 US patients with locoregional gastric cancer. Genomic DNA was analyzed for association of 11 SNPs in NFKB1, RELA, CCL2, and CCR2 with clinical outcome using PCR-based direct DNA sequencing. RESULTS: The univariable analysis showed four SNPs had significant association with clinical outcome in the Japanese cohort, NFKB1 rs230510 remained significant upon multivariable analysis. The patients with the A allele of the NFKB1 rs230510 had significantly longer overall survival (OS) compared with those with the T/T genotype in both the Japanese and US cohort in the univariable analysis. In contrast, genotypes with the T allele of CCL2 rs4586 were significantly associated with shorter OS compared with the C/C genotype in the US cohort [hazard ratio (HR) 2.43; P = 0.015] but longer OS in the Japanese cohort (HR 0.58; P = 0.021), resulting in the statistically significant opposite impact on OS (P = 0.001). CONCLUSIONS: Our study provides the first evidence that the NFKB1 rs230510 and CCL2 rs4586 are significantly associated with the clinical outcome in patients with locoregional gastric cancer. These results also suggest that the genetic predisposition of the host may dictate the immune-related component of the tumor for progression in gastric cancer.
Assuntos
Quimiocina CCL2/genética , Macrófagos/imunologia , NF-kappa B/genética , Receptores CCR2/genética , Neoplasias Gástricas/genética , Fator de Transcrição RelA/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Modelos de Riscos Proporcionais , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/mortalidadeRESUMO
The majority of malignant mesothelioma possesses the wild-type p53 gene with a homologous deletion of the INK4A/ARF locus containing the p14(ARF) and the p16(INK4A) genes. We examined whether forced expression of p53 inhibited growth of mesothelioma cells and produced anti-tumor effects by a combination of cisplatin (CDDP) or pemetrexed (PEM), the first-line drugs for mesothelioma treatments. Transduction of mesothelioma cells with adenoviruses bearing the p53 gene (Ad-p53) induced phosphorylation of p53, upregulated Mdm2 and p21 expression levels and decreased phosphorylation of pRb. The transduction generated cleavage of caspase-8 and -3, but not caspase-9. Cell cycle analysis showed increased G0/G1- or G2/M-phase populations and subsequently sub-G1 fractions, depending on cell types and Ad-p53 doses. Transduction with Ad-p53 suppressed viability of mesothelioma cells and augmented the growth inhibition by CDDP or PEM mostly in a synergistic manner. Intrapleural injection of Ad-p53 and systemic administration of CDDP produced anti-tumor effects in an orthotopic animal model. These data collectively suggest that Ad-p53 is a possible agent for mesothelioma in combination with the first-line chemotherapeutics.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Genes p53 , Mesotelioma/tratamento farmacológico , Mesotelioma/metabolismo , Proteína Supressora de Tumor p53/biossíntese , Adenoviridae/genética , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Caspases/metabolismo , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/fisiologia , Cisplatino/administração & dosagem , Ativação Enzimática , Feminino , Glutamatos/administração & dosagem , Guanina/administração & dosagem , Guanina/análogos & derivados , Humanos , Mesotelioma/genética , Mesotelioma/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pemetrexede , Fosforilação , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
We reviewed aortic root disease and operative procedures. Between January 1982 and December 2008, aortic root operation was performed for 58 patients with various aortic root disease. We chose Bentall type operations in extensive root destructive cases and urgent or reoperative cases. Overall in-hospital mortality was 8.6% (5/58). Four patients (7.5% of survivors) died during the period of followup. Actuarial survival at 15 years was 92%. Freedom from cardiovascular event at 10 and 15 years was 81% and 27%, respectively. Of 5 reoperations in 5 patients, only 1 was required due to complications of the initial Bentall type operation. The Bentall type operations resulted in a durable result. Although, in Marfan syndrome, freedom from cardiovascular event was lower than that in non-Marfan syndrome, actuarial survival rate was equal with non-Marfan syndrome. Close observation is necessary for detecting cardiovascular event, especially in Marfan syndrome.
Assuntos
Doenças da Aorta/cirurgia , Procedimentos Cirúrgicos Cardiovasculares/métodos , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
SUMMARY: We describe a very rare case of anomalous origin of the anterior choroidal artery. In our case the anterior choroidal artery arises from the internal carotid artery proximal to the posterior communicating artery.
RESUMO
A 14-day-old, 2,042 g neonate with interrupted aortic arch (IAA) type B was admitted to our hospital because of respiratory failure. Although alprostadil and alprostadil alfadex were used to keep the ductus arteriosus open, her congestive heart failure became worse and anuria and metabolic acidosis started to appear. We performed single-stage repair for her at 14 days old. Continuous hemodiafiltration (CHDF) was initiated immediately after the operation and peritoneal dialysis was started after paralytic ileus improved. CHDF improved her renal function and she was discharged at postoperative day 84. We conclude that CHDF is effective for neonates with acute renal failure although circulation management is rather difficult.
Assuntos
Aorta Torácica/anormalidades , Aorta Torácica/cirurgia , Hemodiafiltração , Feminino , Humanos , Recém-NascidoRESUMO
A 1-month-old girl weighting 3.1 kg was diagnosed as tetralogy of Fallot (TOF) with pulmonary artery atresia (PA) and aberrant right subclavian artery. Before the operation, pulmonary blood flow from a ducus arteriosus was maintained by lipo prostaglandin E1 (PGE1). The patient underwent palliative right ventricular outflow tract reconstruction (pRVOTR) because the proximal aberrant right subclavian artery was stenotic and the ductus arteriosus and branch of the left pulmonary artery were so close. Postoperative course was uneventful and pulmonary artery showed good growth. The pRVOTR as 1st procedure is a useful method for hypoplastic pulmonary artery to get equal and good growth. Although there are controversies about the size of right ventricular outflow tract (RVOT), 5 or 6 mm diameter of RVOT is recommended for the operative repair of hypoplastic left heart syndrome. We concluded that the pRVOTR should be one of the options as 1st palliative procedure for TOF with PA and diminutive pulmonary artery.
Assuntos
Anormalidades Múltiplas/cirurgia , Procedimentos Cirúrgicos Cardiovasculares/métodos , Cuidados Paliativos , Atresia Pulmonar/cirurgia , Artéria Subclávia/anormalidades , Tetralogia de Fallot/cirurgia , Feminino , Ventrículos do Coração/cirurgia , Humanos , Recém-Nascido , Artéria Pulmonar/cirurgiaRESUMO
EPR spectra of the excited quartet and doublet molecular states of (tetraphenylporphinato)zinc(II) covalently bounded to 3-(N-nitronyl-notroxide) pyridine stable radical are modeled in terms of the spin-Hamiltonian given by the sum of the contributions from the radical and triplet moieties, and the interaction between them. The later is represented by anisotropic point dipolar and isotropic exchange electron spin-spin interactions. It is shown that the high field (W-band) EPR spectra depend on energy separation between the electronic doublet (D) and quartet (Q) states. This dependence was utilized to estimate the upper limit of the intensity of exchange interaction between the radical and porphyrin moieties.
Assuntos
Metaloporfirinas/química , Porfirinas/química , Marcadores de Spin , Simulação por Computador , Espectroscopia de Ressonância de Spin Eletrônica , Conformação Molecular , Termodinâmica , Fatores de TempoRESUMO
BACKGROUND AND PURPOSE: The inferior petrosal sinus (IPS) is the main transvenous access route used to examine or treat lesions involving the cavernous sinus. To carry out these procedures successfully, one must have a detailed knowledge of the anatomy of the venous system around the junction of the IPS and the internal jugular vein (IJV). MATERIALS AND METHODS: Eighty-three sides in 63 patients (26 men, 37 women; mean, 56.5 years of age) were examined by using 3D rotational venography (3DRV). RESULT: The drainage patterns of the IPS could be classified into the following 6 types, with emphasis on the level of IPS-IJV junction: type A, the IPS drains into the jugular bulb in 1/83 sides (1.2%); type B, the IPS drains into the IJV at the level of the extracranial opening of the hypoglossal canal in 29/83 sides (34.9%); type C, the IPS drains into the lower extracranial IJV in 31/83 sides (37.3%); type D, the IPS forms a plexus and has multiple junctions to the IJV near the jugular foramen in 5/83 sides (6.0%); type E, the IPS drains directly into the vertebral venous plexus (VVP) with no connection to the IJV in 3/83 sides (3.6%); and type F, the IPS is absent in 14/83 sides (16.9%). Each type is also characterized by the way of anastomosis with the VVP. CONCLUSION: This classification seemed to be rational from the embryologic viewpoint, and it may be useful in establishing treatment strategies that involve endovascular manipulation via the IPS.
Assuntos
Cavidades Cranianas/anatomia & histologia , Cavidades Cranianas/diagnóstico por imagem , Imageamento Tridimensional/métodos , Flebografia/métodos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Rotação , Sensibilidade e EspecificidadeRESUMO
We report a rare case of acquired left ventricular-right atrial communication resulting from infective endocarditis. A 57-year-old male with aortic regurgitation due to infective endocarditis was referred to our hospital because of severe congestive heart failure. Preoperative transthoracic echocardiography showed aortic, mitral and tricuspid severe regurgitations. Intraoperative transesophageal echocardiography revealed left ventricular-right atrial shunt. The fistula was located at the atrioventricular membranous septum. The communication site from the left view was below the commissure between the right coronary cusp and non-coronary cusp, and from the right view was just above the tricuspid annulus of the septal leaflet. The fistula was closed directly with mattress suture and aortic valve replacement and both mitral and tricuspid ring annuloplasty were carried out simultaneously. The postoperative course was uneventful. It is important to inspect shunts carefully in echocardiography of infective endocarditis with massive regurgitations.